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https://www.readbyqxmd.com/read/28430840/checkpoint-dependent-phosphorylation-of-med1-trap220-in-response-to-dna-damage
#1
Hyun-Ju Kim, Jeanho Yun
Mediator complex subunit 1 (Med1)/Thyroid hormone receptor-associated protein 220 (TRAP220), an essential component of thyroid hormone receptor-associated proteins (TRAP)/mediator, plays important roles in hormone responses and tumorigenesis. However, the role of Med1 in the DNA damage response has not been studied. In this study, we found that DNA damage, resulted from γ-irradiation, ultraviolet (UV)-irradiation, or hydroxyurea, induced phosphorylation of Med1 in vivo. Phosphorylation of Med1 was abrogated by either caffeine or wortmannin treatment, suggesting that Med1 is phosphorylated through the DNA damage checkpoint pathway...
April 19, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28420694/caffeine-preferentially-protects-against-oxygen-induced-retinopathy
#2
Shuya Zhang, Rong Zhou, Bo Li, Haiyan Li, Yanyan Wang, Xuejiao Gu, Lingyun Tang, Cun Wang, Dingjuan Zhong, Yuanyuan Ge, Yuqing Huo, Jing Lin, Xiao-Ling Liu, Jiang-Fan Chen
Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice...
April 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28403410/assessing-the-pathogenicity-of-ryr1-variants-in-malignant-hyperthermia
#3
A Merritt, P Booms, M-A Shaw, D M Miller, C Daly, J G Bilmen, K M Stowell, P D Allen, D S Steele, P M Hopkins
Background: . Missense variants in the ryanodine receptor 1 gene ( RYR1 ) are associated with malignant hyperthermia but only a minority of these have met the criteria for use in predictive DNA diagnosis. We examined the utility of a simplified method of segregation analysis and a functional assay for determining the pathogenicity of recurrent RYR1 variants associated with malignant hyperthermia. Methods: . We identified previously uncharacterised RYR1 variants found in four or more malignant hyperthermia families and conducted simplified segregation analyses...
April 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28390800/ca-2-release-via-two-pore-channel-type-2-tpc2-is-required-for-slow-muscle-cell-myofibrillogenesis-and-myotomal-patterning-in-intact-zebrafish-embryos
#4
Jeffrey J Kelu, Sarah E Webb, John Parrington, Antony Galione, Andrew L Miller
We recently demonstrated a critical role for two-pore channel type 2 (TPC2)-mediated Ca(2+) release during the differentiation of slow (skeletal) muscle cells (SMC) in intact zebrafish embryos, via the introduction of a translational-blocking morpholino antisense oligonucleotide (MO). Here, we extend our study and demonstrate that knockdown of TPC2 with a non-overlapping splice-blocking MO, knockout of TPC2 (via the generation of a tpcn2(dhkz1a) mutant line of zebrafish using CRISPR/Cas9 gene-editing), or the pharmacological inhibition of TPC2 action with bafilomycin A1 or trans-ned-19, also lead to a significant attenuation of SMC differentiation, characterized by a disruption of SMC myofibrillogenesis and gross morphological changes in the trunk musculature...
April 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28387457/dampened-activity-of-ryanodine-receptor-channels-in-mutant-skeletal-muscle-lacking-tric-a
#5
Sam El-Ajouz, Elisa Venturi, Katja Witschas, Matthew Beech, Abigail D Wilson, Chris Lindsay, David Eberhardt, Fiona O'Brien, Tsunaki Iida, Miyuki Nishi, Hiroshi Takeshima, Rebecca Sitsapesan
TRIC-A is a major component of the nuclear and sarcoplasmic reticulum (SR) membranes of cardiac and skeletal muscle, and is localised closely with RyR channels in the SR terminal cisternae. The skeletal muscle of Tric-a KO mice is characterised by Ca(2+) overloaded and swollen SR and by changes in the properties of SR Ca(2+) release. We therefore investigated if RyR1 gating behaviour is modified in the SR from Tric-a KO mice by incorporating native RyR1 into planar phospholipid bilayers under voltage-clamp conditions...
April 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28375845/effect-of-adrenocorticotropic-hormone-on-ucp1-gene-expression-in-brown-adipocytes
#6
Hirendra M Biswas
BACKGROUND: Like other tissues, adrenocorticotropic hormone (ACTH) can produce its effect on brown adipose tissue (BAT). This study was taken to understand the direct effect of ACTH action on thermogenin gene expression and possible relation with α receptors and caffeine with this hormone. METHODS: Brown fat precursor cells were isolated from interscapular BAT of young mice and grown in culture. The cells were exposed to norepinephrine (NE) and other agents. Total RNA was isolated after harvesting the cells, and northern blot analysis was performed...
April 4, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28352352/combination-therapy-with-catechins-and-caffeine-inhibits-fat-accumulation-in-3t3-l1-cells
#7
Xiaojuan Zhu, Licong Yang, Feng Xu, Lezhen Lin, Guodong Zheng
Catechins and caffeine, which are green tea components, have a slimming effect; however, the combinational effect of fat metabolism in 3T3-L1 cells remains unclear. In the present study, 3T3-L1 cells were treated with catechins and caffeine in combination, and it was found that combination therapy with catechins and caffeine markedly reduced intracellular fat accumulation, mRNA expression levels of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α in the early stage of cell differentiation were significantly reduced, and mRNA expression of fatty acid synthetase(FAS) andglycerol-3-phosphate dehydrogenase protein expression levels of FAS were downregulated...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28350110/glutamate%C3%A2-mediated-effects-of-caffeine-and-interferon%C3%A2-%C3%AE-on-mercury-induced-toxicity
#8
Ayse Basak Engin, Evren Doruk Engin, Kirill Golokhvast, Demetrios A Spandidos, Aristides M Tsatsakis
The molecular mechanisms mediating mercury‑induced neurotoxicity are not yet completely understood. Thus, the aim of this study was to investigate whether the severity of MeHg‑ and HgCl2‑mediated cytotoxicity to SH‑SY5Y human dopaminergic neurons can be attenuated by regulating glutamate‑mediated signal‑transmission through caffeine and interferon‑γ (IFN‑γ). The SH‑SY5Y cells were exposed to 1, 2 and 5 µM of either MeHgCl2 or HgCl2 in the presence or absence of L‑glutamine. To examine the effect of adenosine receptor antagonist, the cells were treated with 10 and 20 µM caffeine...
March 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28335379/the-role-of-adenosine-signaling-in-headache-a-review
#9
REVIEW
Nathan T Fried, Melanie B Elliott, Michael L Oshinsky
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments...
March 13, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28320167/caffeine-creatine-grin2a-and-parkinson-s-disease-progression
#10
David K Simon, Cai Wu, Barbara C Tilley, Katja Lohmann, Christine Klein, Haydeh Payami, Anne-Marie Wills, Michael J Aminoff, Jacquelyn Bainbridge, Richard Dewey, Robert A Hauser, Susen Schaake, Jay S Schneider, Saloni Sharma, Carlos Singer, Caroline M Tanner, Daniel Truong, Peng Wei, Pei Shieen Wong, Tianzhong Yang
Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28294567/growth-hormone-secretagogues-prevent-dysregulation-of-skeletal-muscle-calcium-homeostasis-in-a-rat-model-of-cisplatin-induced-cachexia
#11
Elena Conte, Giulia Maria Camerino, Antonietta Mele, Michela De Bellis, Sabata Pierno, Francesco Rana, Adriano Fonzino, Roberta Caloiero, Laura Rizzi, Elena Bresciani, Khoubaib Ben Haj Salah, Jean-Alain Fehrentz, Jean Martinez, Arcangela Giustino, Maria Addolorata Mariggiò, Mauro Coluccia, Domenico Tricarico, Marcello Diego Lograno, Annamaria De Luca, Antonio Torsello, Diana Conte, Antonella Liantonio
BACKGROUND: Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain...
March 10, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28290972/malignant-hyperthermia-susceptibility-and-fitness-for-duty
#12
Michael A Lee, Erin B McGlinch, Maria C McGlinch, John F Capacchione
INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28264466/synthesis-and-characterization-of-a-new-bivalent-ligand-combining-caffeine-and-docosahexaenoic-acid
#13
Víctor Fernández-Dueñas, Jhonny Azuaje, Xavier Morató, Begoña Cordobilla, Joan Carles Domingo, Eddy Sotelo, Francisco Ciruela
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine...
February 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28263415/very-low-concentrations-of-ethanol-suppress-excitatory-synaptic-transmission-in-rat-visual-cortex
#14
Lucas Luong, Nicholas M Bannon, Andrew Redenti, Marina Chistiakova, Maxim Volgushev
Ethanol is one of the most commonly used substances in the world. Behavioral effects of alcohol are well described, however cellular mechanisms of its action are poorly understood. There is an apparent contradiction between measurable behavioral changes produced by low concentrations of ethanol, and lack of evidence of synaptic changes at these concentrations. Further, effects of ethanol on synaptic transmission in the neocortex are poorly understood. Here we set to determine effects of ethanol on excitatory synaptic transmission in the neocortex...
March 6, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28257435/idelalisib-and-caffeine-reduce-suppression-of-t-cell-responses-mediated-by-activated-chronic-lymphocytic-leukemia-cells
#15
Barry D Hock, Sean A MacPherson, Judith L McKenzie
Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28251715/homeostatic-response-to-sleep-rest-deprivation-by-constant-water-flow-in-larval-zebrafish-in-both-dark-and-light-conditions
#16
Vilma Aho, Maija Vainikka, Henri A J Puttonen, Heidi M K Ikonen, Tiia Salminen, Pertti Panula, Tarja Porkka-Heiskanen, Henna-Kaisa Wigren
Sleep-or sleep-like states-have been reported in adult and larval zebrafish using behavioural criteria. These reversible quiescent periods, displaying circadian rhythmicity, have been used in pharmacological, genetic and neuroanatomical studies of sleep-wake regulation. However, one of the important criteria for sleep, namely sleep homeostasis, has not been demonstrated unequivocally. To study rest homeostasis in zebrafish larvae, we rest-deprived 1-week-old larvae with a novel, ecologically relevant method: flow of water...
March 2, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28250576/having-a-coffee-break-the-impact-of-caffeine-consumption-on-microglia-mediated-inflammation-in-neurodegenerative-diseases
#17
REVIEW
Maria H Madeira, Raquel Boia, António F Ambrósio, Ana R Santiago
Caffeine is the major component of coffee and the most consumed psychostimulant in the world and at nontoxic doses acts as a nonselective adenosine receptor antagonist. Epidemiological evidence suggests that caffeine consumption reduces the risk of several neurological and neurodegenerative diseases. However, despite the beneficial effects of caffeine consumption in human health and behaviour, the mechanisms by which it impacts the pathophysiology of neurodegenerative diseases still remain to be clarified. A promising hypothesis is that caffeine controls microglia-mediated neuroinflammatory response associated with the majority of neurodegenerative conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28235548/chronic-and-acute-adenosine-a2a-receptor-blockade-prevents-long-term-episodic-memory-disruption-caused-by-acute-cannabinoid-cb1-receptor-activation
#18
Francisco M Mouro, Vânia L Batalha, Diana G Ferreira, Joana E Coelho, Younis Baqi, Christa E Müller, Luísa V Lopes, Joaquim A Ribeiro, Ana M Sebastião
Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB1 receptor (CB1R)-induced memory deficits through an adenosine A1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A2A receptors (A2ARs) affects long-term episodic memory deficits induced by a single injection of a selective CB1R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i...
February 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28215251/the-association-between-caffeine-consumption-and-objective-sleep-variables-is-dependent-on-adora2a-c-1083t-c-genotypes
#19
Rafael Almeida Nunes, Diego Robles Mazzotti, Camila Hirotsu, Monica L Andersen, Sergio Tufik, Lia Bittencourt
OBJECTIVE: To verify the association between c.1083T>C polymorphism in the adenosine receptor A2A gene (ADORA2A) and objective sleep, as well as the correlation between caffeine consumption, sleep parameters, and electroencephalographic spectral power in a large, population-based sample from São Paulo, Brazil. METHODS: This study was conducted in participants of the São Paulo Epidemiologic Sleep Study (EPISONO), a large, population-based survey consisting of a representative sample of the inhabitants of the city from São Paulo, Brazil, according to sex, age (20-80 years), and socioeconomic status in the year 2007...
February 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28202385/long-term-consequences-of-disrupting-adenosine-signaling-during-embryonic-development
#20
REVIEW
Scott A Rivkees, Christopher C Wendler
There is growing evidence that disruption in the prenatal environment can have long-lasting effects on an individual's health in adulthood. Research on the fetal programming of adult diseases, including cardiovascular disease, focuses on epi-mutations, which alter the normal pattern of epigenetic factors such as DNA methylation, miRNA expression, or chromatin modification, rather than traditional genetic alteration. Thus, understanding how in utero chemical exposures alter epigenetics and lead to adult disease is of considerable public health concern...
February 13, 2017: Molecular Aspects of Medicine
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